Articular cartilage is a type of hyaline cartilage that lines the surfaces of the opposing bones in a diarthrodal joint (e.g. knee, hip, shoulder, etc.). Articular cartilage provides a near frictionless articulation between the bones, while also functioning to absorb and transmit the compressive and shear forces encountered in the joint. Further, since the tissue associated with articular cartilage is aneural, these load absorbing and transmitting functions occur in a painless fashion in a healthy joint.
Human joints also have another type of cartilage present: intra-articular fibrocartilage. Intra-articular fibrocartilage can be present in the form of a discus articularis, that is, as a plate or ring of fibrocartilage in the joint capsule separating the joint surfaces (articular cartilage) of the bones of the joint. Such fibrocartilage is present, for example, in the temporomandibular joint, between vertebrae, and in the knee joint. In the knee joint, the intra-articular fibrocartilage comprises the meniscus, a crescent-shaped or semi-lunar-shaped disc of tissue that is located between the femoral condyles and the tibial plateau. The meniscus primarily functions as a shock absorber, absorbing the shock of compressive and shear forces in the knee. The meniscus also provides a substantially frictionless surface for articulation of the knee joint.
When cartilage tissue is no longer healthy, there can be debilitating pain in the joint. Cartilage health can be adversely affected by disease, aging, or trauma. The adverse effects of disease, aging and trauma can be in the form of a tear in the cartilage or in the form of a breakdown of the cartilage matrix.
In the knee, the meniscus is frequently damaged in twisting injuries. It is also damaged with repetitive impact over time. Meniscus degeneration can also occur by aging; as a person ages, the meniscus can become soft in places, so that even common motions like squatting can cause meniscal tears. Such degenerative or traumatic tears to the meniscus, which result in partial or complete loss of function, frequently occur in the white-white zone of the meniscus. Such tears result in unstable flaps of meniscal tissue in the knee joint causing, in the short term, severe joint pain and locking, and in the long term, a loss of mechanical function leading to osteoarthritis.
Common surgical procedures for treating meniscal damage include tear repairs and menisectomies. A tear repair is most commonly performed when the tear is a clean longitudinal vertical lesion in the vascular red zone of the meniscus. The basic strategy is to stabilize the tear by limiting or eliminating radial separation of the faces of the tear when the meniscus is load bearing. Many devices and surgical procedures exist for repairing meniscal tears by approximating the faces of the meniscus at the tear. Examples of such devices and procedures are disclosed in the following U.S. Pat. Nos.: 6,319,271; 6,306,159; 6,306,156; 6,293,961; 6,156,044; 6,152,935; 6,056,778; 5,993,475; 5,980,524; 5,702,462; 5,569,252; 5,374,268; 5,320,633; and 4,873,976.
Menisectomies involve the surgical removal of part of the meniscus. Such procedures have generally been performed in cases of radial tears, horizontal tears, vertical longitudinal tears outside the vascular zone, complex tears, or defibrillation. Although menisectomies provide immediate relief to the patient, in the long term the absence of part of the meniscus can cause cartilage wear on the condylar surface, eventually leading to arthritic conditions in the joint. And when the resected tissue is from the avascular, white-white zone, the meniscus has little potential for self-regeneration. Thus, removal of meniscal tissue from the avascular white-white zone can result in partial or permanent loss of meniscal tissue, making the joint susceptible to osteoarthritis.
Attempts have been made to regenerate meniscal tissue following a menisectomy. Previous attempts have included the use of surgical techniques and implants. The surgical techniques have been used to provide vascularity to the avascular region through synovial abrasion or by providing vascular access channels. Implants have included fibrin clot, meniscal allografts (see Stollsteimer, G. T., et al., “Meniscal allograft transplantation: a 1-to 5-year follow-up of 22 patients,” Arthroscopy, 16(4): pp 343-7 (2000); Rodeo, S. A., “Meniscal allografts—where do we stand,” Am J Sports Med, 29(2): pp. 246-61 (2001)), synthetic biodegradable polymer implants (with or without cells), a collagen scaffold device made at least in part from purified natural fibers that are cross-linked to form the device and scaffolds made from synthetic polymers.
A scaffold device made from purified collagen is described in U.S. Pat. No. 6,042,610. The following U.S. Patents also disclose a meniscal augmentation device for a damaged meniscus: U.S. Pat. Nos. 5,735,903; 5,681,353; 5,306,311; 5,108,438; 5,007,934; and 4,880,429. All of these patents are incorporated by reference herein.
A scaffold device made from a synthetic polymer is described by Klompmaker, J., et al. in “Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog,” Biomaterials, 17(2): pp 1169-75 (1996) and by deGroot, J. H., et al., “Use of porous polyurethanes for meniscal reconstruction and mensical prostheses,” Biomaterials, 17(2): pp. 163-73 (1996). Medical applications for synthetic polymers are also disclosed in patents and patent applications, such as, for example, U.S. Pat. Nos. 6,224,892; 5,847,012 and 5,677,355.
The previous attempts at regenerating meniscal tissue have been problematic. While providing vascularity at the site of meniscal lesions may work well for more stable meniscal tears where very little tissue has been lost, providing vascularity where there is significant tissue loss (for example, due to menisectomy) has not consistently resulted in an acceptable outcome. See Arnoczky, S. P. and R. F. Warren, “The microvasculature of the meniscus and its response to injury. An experimental study in the dog, Am J Sports Med, 11(3): p.131-41 (1983); Fox, J. M., K. G. Rintz. and R. D. Ferkel, “Trephination of incomplete meniscal tears,” Arthroscopy, 9(4): p. 451-5 (1993). Although autologous fibrin clot can be effective in regenerating critical sized defects, Arnoczky, S. P., R. F. Warrren, and J. M. Spivak, “Meniscal repair using an exogeneous fibrin clot. An experimental study in dogs,” J Bone Joint Surg Am, 70(8): pp1209-17 (1988). The fragility of a fibrin clot presents clinical challenges in handling and securing the fibrin clot to the meniscal body to obtain a sufficiently long time-of-residence. Rode, S. A., “Arthroscopic meniscal repair with use of the outside-in technique,” Instr Course Lect, 49, pp 195-206 (2000).
With meniscal allografts, there is a risk of disease transfer, poor revascularization, and infiltration and breaking down by host cells resulting in joint instability. In addition, the new tissue replacing the allograft may not be of sufficient quality to restore normal function. See: Sweigart, M. A. and K. A. Athanasiou, “Toward tissue engineering of the knee meniscus,” Tissue Eng., 7(2) pp 111-29 (2001); Boss, A., J. Klimkiewicz and F. H. Fu, “Technical innovation: creation of a peripheral vascularized trough to enhance healing in cryopreserved meniscal allograft reconstruction,” Knee Surg Sports Traumatol Arthrosc, 8(3): pp 159-62 (2000); Siegel, M. G. and C. S. Roberts, “Meniscal allografts,” Clin Sports Med,” 1291: pp 59-80 (1993).
Other meniscal implants may be difficult to handle during surgery and fixation or have insufficient mechanical properties for a sufficient time-of-residence in vivo.
It is also known to use naturally occurring extracelluar matrices (ECMs) to provide a scaffold for tissue repair and regeneration. One such ECM is small intestine submucosa (SIS). SIS has been described as a natural biomaterial used to repair, support, and stabilize a wide variety of anatomical defects and traumatic injuries. The SIS material is derived from porcine small intestinal submucosa that models the qualities of its host when implanted in human soft tissues. Further, it is taught that the SIS material provides a natural matrix with a three-dimensional structure and biochemical composition that attracts host cells and supports tissue remodeling. SIS products, such as OASIS.™ and SURGISIS.™, are commercially available from Cook Biotech Inc., Bloomington, Ind.
Another SIS product, RESTORE.® Orthobiologic Implant, is available from DePuy Orthopaedics, Inc. in Warsaw, Ind. The DePuy product is described for use during rotator cuff surgery, and is provided as a resorbable framework that allows the rotator cuff tendon to regenerate. The RESTORE Implant is derived from porcine small intestine submucosa, a naturally occurring ECM composed primarily of collagenous proteins, that has been cleaned, disinfected, and sterilized. Other biological molecules, such as growth factors, glycosaminoglycans, etc., have also been identified in SIS. See: Hodde et al., Tissue Eng., 2(3): 209-217 (1996); Voytik-Harbin et al., J. Cell. Biochem., 67: 478-491 (1997); McPherson and Badylak, Tissue Eng., 4(1): 75-83 (1998); Hodde et al., Endothelium 8(1): 11-24; Hodde and Hiles, Wounds, 13(5): 195-201 (2001); Hurst and Bonner, J. Biomater. Sci. Polym. Ed., 12(11): 1267-1279 (2001); Hodde et al., Biomaterial, 23(8): 1841-1848 (2002); and Hodde, Tissue Eng., 8(2): 295-308 (2002). During nine years of preclinical testing in animals, there were no incidences of infection transmission from the implant to the host, and the RESTORE.® Orthobiologic Implant has not adversely affected the systemic activity of the immune system. See: Allman et al., Transplant, 17(11): 1631-1640 (2001); Allman et al., Tissue Eng., 8(1):53-62 (2002).
While small intestine submucosa is available, other sources of submucosa are known to be effective for tissue remodeling. These sources include, but are not limited to, stomach, bladder, alimentary, respiratory, and genital submucosa. In addition, liver basement membrane is known to be effective for tissue remodeling. See, e.g., U.S. Pat. Nos. 6,379,710, 6,171,344, 6,099,567, and 5,554,389, hereby incorporated by reference. Further, while ECM is most often porcine derived, it is known that these various ECM materials can be derived from non-porcine sources, including bovine and ovine sources. Additionally, the ECM material may also include partial layers of the lamina propria, muscularis mucosa, stratum compactum, submucosal plexuses, and vascular submucosa and/or other tissue materials depending upon factors such as the source from which the ECM material was derived and the delamination procedure.
The following patents, hereby incorporated by reference, disclose the use of ECMs for the regeneration and repair of various tissues: U.S. Pat. Nos. 6,379,710; 6,187,039; 6,176,880; 6,126,686; 6,099,567; 6,096,347; 5,997,575; 5,993,844; 5,968,096; 5,955,110; 5,922,028; 5,885,619; 5,788,625; 5,733,337; 5,762,966; 5,755,791; 5,753,267; 5,711,969; 5,645,860; 5,641,518; 5,554,389; 5,516,533; 5,460,962; 5,445,833; 5,372,821; 5,352,463; 5,281,422; and 5,275,826.